An ischemic stroke is a time-sensitive event where a blood clot blocks blood flow to the brain, requiring rapid imaging to determine which brain tissue is still viable. Computed Tomography Perfusion (CTP) is a quick and widely available technique that helps clinicians assess the physiological impact of the blockage. CTP moves beyond simply identifying the clot to quantifying the extent of brain damage and the amount of tissue that can potentially be saved. It provides a detailed picture of blood flow dynamics to guide emergency treatment decisions.
Understanding CT Perfusion Imaging
CT Perfusion is a dynamic imaging method that involves injecting a contrast agent, typically an iodine-based dye, into a patient’s vein while performing rapid, sequential CT scans of the brain. The scanner measures how the contrast material flows into and out of the brain tissue over time, allowing specialized software to generate detailed maps of blood flow. These maps quantify various hemodynamic parameters, which are the fundamental measurements of blood delivery and speed.
The three primary measurements derived from CTP are Cerebral Blood Flow (CBF), Cerebral Blood Volume (CBV), and Mean Transit Time (MTT) or Time to Maximum (Tmax). CBF is the volume of blood passing through brain tissue per minute, and CBV is the total volume of blood within that tissue’s vascular network. MTT measures the average time blood takes to pass through capillaries. Tmax indicates the time for the contrast material to reach its maximum concentration, often marking delayed blood delivery. These parameters provide the raw data for determining tissue viability.
Identifying the Ischemic Core and Penumbra
The hemodynamic data derived from CTP is used to identify two distinct tissue zones: the ischemic core and the penumbra, which together make up the total area affected by reduced blood flow. The ischemic core is the region of the brain that has experienced such a severe and prolonged lack of blood flow that the tissue is considered irreversibly damaged. This area is typically defined on CTP maps by a severe reduction in both Cerebral Blood Flow and Cerebral Blood Volume.
The penumbra, or salvageable tissue, is the surrounding area of hypoperfused brain that is impaired but not yet dead. This tissue receives just enough collateral blood flow to remain viable, making it the primary target for reperfusion therapies. The poor flow results in prolonged transit time, seen as a significant increase in Tmax or MTT. Crucially, the Cerebral Blood Volume in the penumbra is often preserved or only minimally reduced, indicating that vessels are still open if the blockage is removed.
To distinguish these zones, specific physiological thresholds are applied to the CTP measurements. The ischemic core is commonly defined by a relative Cerebral Blood Flow (rCBF) that is less than 30% of the healthy, unaffected side of the brain. The penumbra is defined by the total volume of tissue with a significant delay in blood arrival, often measured using a Tmax threshold of greater than six seconds.
Calculating the Mismatch Ratio
The Mismatch Ratio is a quantitative metric used to assess the potential for recovery by comparing the volume of the penumbra to the ischemic core. Calculated by automated software, the ratio is defined as the total hypoperfused volume (penumbra plus core) divided by the volume of the ischemic core: Mismatch Ratio = (Volume of Hypoperfused Tissue) / (Volume of Ischemic Core).
A high mismatch ratio suggests a favorable profile, often called a “Target Mismatch,” indicating that the volume of salvageable penumbra is significantly larger than the irreversibly damaged core. A ratio of 1.8 or greater is a common clinical threshold, meaning the total hypoperfusion area is at least 1.8 times the size of the core. This suggests a substantial amount of tissue is still at risk and could be saved if blood flow is restored quickly.
Conversely, a low mismatch ratio, approaching 1.0, is termed a “Non-Target Mismatch.” This profile suggests that the stroke is already “completed,” meaning the ischemic core is nearly the same size as the total hypoperfused area, and little to no viable penumbra remains. In these cases, the potential for a positive outcome from revascularization treatment is significantly reduced because the majority of the affected tissue is already dead.
How the Mismatch Ratio Guides Emergency Treatment
The mismatch ratio is a primary factor in determining which acute ischemic stroke patients are candidates for mechanical thrombectomy (surgical clot removal). The ratio allows clinicians to move beyond a strict time-based window, adopting a “time is tissue” approach based on the biological status of the brain. Patients with a favorable mismatch profile (a high ratio) are likely to benefit because they have a large volume of salvageable brain tissue.
This concept was validated by landmark clinical trials, particularly the DAWN and DEFUSE 3 studies, which established criteria for treating patients outside the traditional six-hour window.
Landmark Clinical Trials
The DEFUSE 3 trial required a perfusion mismatch ratio of 1.8 or greater and a penumbra volume of at least 15 milliliters. This allowed selection of patients for intervention up to 16 hours after stroke onset. The DAWN trial used a related set of criteria, combining the core volume with the clinical deficit. This identified a favorable profile for treatment up to 24 hours after the patient was last known to be well.
The ratio’s use in these trials extended the treatment window for mechanical thrombectomy, allowing more patients to receive a procedure that significantly improves functional outcomes. A patient presenting late with a high mismatch ratio and a small ischemic core is likely a candidate for intervention. Conversely, a patient with a low ratio, even if presenting earlier, may not be offered the procedure due to the high risk of complications without significant benefit. The mismatch ratio transforms the treatment decision from a time-based judgment into a tissue-based, personalized medical assessment.